Project Summary/Abstract This application proposes a randomized double-blind placebo controlled trial of the use of glucocorticoids to improve the clinical course of neonates following cardiac surgery. Cardiopulmonary bypass (CPB) is critical to cardiac surgery, but the pathophysiologic processes engendered by CPB play an important role in post- operative recovery. The use, doses and schedule of glucortocoid administration to ameliorate these CPB induced processes is highly variable and without clear data to provide direction. The Primary Aim of this study is to compare the effects of intraoperative methypredisolone to placebo on a composite morbidity-mortalitiy outcome following neonatal CPB. Secondary Endpoints include: inotropic requirements, incidence of low cardiac output syndrome, fluid balance, ICU stay parameters, levels of inflammatory molecules, neuro- developmental outcomes, and safety parameters. The study will focus on neonates because their post-CPB clinical course is typically more severe, and that high level of severity itself provides a substrate for identifying the positive effects of a particular therapy. Finally, a therapy identified as beneficial has the greatest potential for benefit in this vulnerable population. A unique aspect of the protocol is the use of a novel multiplexer technology which allows analysis of a broad array of cytokines, matrix metalloproteinases and microribonucleic acids from a sample of one milliliter or less of whole blood. The results of this study should clearly define the clinical utility of steroids and help determine the mechanisms for any observed effect. Based on the frequency of complex congenital heart defects, the incidence of the low cardiac output, and the daily costs of ICU care, a reduction in postoperative morbidity can be estimated to decrease total healthcare expenditures in the US by hundreds of millions of dollars annually.